Alzheimer's disease (AD) is the most common form of dementia. Most often, it is diagnosed in people over 65 years of age, although the less-prevalent early-onset Alzheimer's can occur much earlier. In 2006, there were 26.6 million sufferers worldwide. Alzheimer's is predicted to affect 1 in 85 people globally by 2050. The earliest observable symptoms are often mistakenly thought to be ‘age-related’ concerns, or manifestations of stress. In the early stages, the most commonly recognised symptom is inability to acquire new memories, such as difficulty in recalling recently observed facts.
As the disease advances, gradually, bodily functions are lost, ultimately leading to death. Individual prognosis is difficult to assess, as the duration of the disease varies. AD develops for an indeterminate period of time before becoming fully apparent, and it can progress undiagnosed for years. The mean life expectancy following stage 2 diagnosis is approximately seven years. Fewer than three percent of individuals live more than fourteen years after diagnosis. In developed countries, AD is one of the most costly diseases to society.
A 2004 study tried to explain the causes of the AD and found that deposition of amyloid plaques does not correlate well with neuron loss. This observation supports the tau hypothesis, the idea that tau protein abnormalities initiate the disease cascade.
Another cause, on which most currently available drug therapies are based, is the cholinergic hypothesis, which proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine. The cholinergic hypothesis has not maintained widespread support, largely because medications intended to treat acetylcholine deficiency have not been very effective. Other cholinergic effects have also been proposed, for example, initiation of large-scale aggregation of amyloid, leading to generalised neuroinflammation.
Four medications are currently approved by regulatory agencies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to treat the cognitive manifestations of AD: three are acetylcholinesterase inhibitors and the other is memantine, an NMDA receptor antagonist. No drug has an indication for delaying or halting the progression of the disease. At present, there is no definitive evidence to support that any particular measure is effective in preventing AD.
The journal “Food chemistry” 116 (2009), pages 470 to 479, relates to the antioxidant, anticholinesterase and antimicrobial constituents from the essential oil and ethanol extract of Salvia potentillifolia.
The journal “Food chemistry” 108 (2008), pages 663 to 668, relates to the inhibitory effect of Turkish Rosmarinus officinalis L. on acetylcholinesterase and butyrylcholinesterase enzymes.
WO 01/68576 relates to dermatological compounds, i.e. novel monocyclic and bicyclic monoterpene diols that stimulate melanogenesis in mammalian skin, hair, wool or fur, and, are useful for treating or preventing various skin and proliferative disorders, neurodegenerative diseases, and diseases regulated by the nitric oxide/cyclic GMP/protein kinase G pathway.
WO 01/68576 can be regarded as representing the closest prior art because it discloses monoterpenes as pharmaceutically active compounds.